tbuckley/cabot-search huggingface dataset:
Association of food insecurity with reduced cancer screening rates.
Authors: Mohammed Masoom Shah, Shahidul Islam, Marc Justin Braunstein
Journal: Journal of Clinical Oncology (2023)

e18609 Background: Social determinants of health, including access to adequate food and nutrition, may influence many aspects of healthcare, including cancer screening. This study explored the associations between food insecurity and cancer screening. Methods: A retrospective analysis was conducted using the National Health Interview Series from 2021 to capture contemporary events. Based on scaled questionnaires, food security was stratified into either food secure or insecure, and then subgrouped into high, marginal, or low security (i.e. most insecure). Associations were made with rates of having at least one screening test. Relationships between variables were evaluated using Chi-Square and Cochran-Armitage trend tests. Logistic regression models were used to find factors associated with cancer screening. Results: Patients included in analyses included: 19,916 for colon, 15,293 for cervical, and 8,589 for prostate cancer screening. Those with food insecurity had significantly lower rates of cancer screening than those with food security across all 3 cancer screens, including for colon (51.3% vs. 61.8% p &lt; 0.0001), cervical (78.1% vs. 85.2% p &lt; 0.0001), and prostate (36.0% vs. 51.5%, p &lt; 0.0001). This was similar when comparing low, marginal, and high food security, respectively, for colonoscopies (50.1% vs. 52.6% vs. 61.8%, p &lt; 0.0001), cervical cancer screening (78% vs. 78.2% vs. 85.1%; p &lt; 0.0001), and prostate-specific antigen testing (31.2% vs. 41.2% vs. 51.5%; p &lt; 0.0001). Other social determinants were analyzed, including insurance type (public vs. private), age, and race. Patients with public health insurance had lower screening rates across all three cancers compared to those with private insurance (p &lt; 0.0001). Lower food security was linked with younger age (p &lt; 0.0001), and Black patients were disproportionately affected by food insecurity compared to other races (p &lt; 0.001). Adjusted for covariates, low food security, minority racial groups, and public insurance were associated with lower odds of cancer screening. Conclusions: Individuals with self-reported food insecurity were found to have lower cancer screening rates than those who were food secure. Further analysis of demographic and clinical information revealed associations between low food security status and public health insurance, younger age, and Black race. These data suggested that measures can be taken to address food insecurity in these populations that appear to be most vulnerable to lacking appropriate cancer screening. [Table: see text]
Perioperative IDO-1 dynamic changes in NSCLC patients.
Authors: Zhijuan Sun, Weiwei Chen, Zhenghao Ye, Sichao Wang, Dazhi Pang, Feng-Ming Spring Kong
Journal: Journal of Clinical Oncology (2023)

e20532 Background: Indoleamine 2,3-dioxygenase (IDO) is an enzyme that is involved in the metabolism of tryptophan, an essential amino acid. It is known to play a role in the regulation of the immune system, and has been linked to perioperative immune status. Specifically, IDO has been shown to be upregulated in the perioperative period, leading to an increased risk of infection and other complications. This is thought to be due to the increased production of kynurenine, a metabolite of tryptophan, which has been associated with immunosuppression. Additionally, IDO has been linked to increased levels of inflammation and oxidative stress, which can further contribute to the risk of complications during surgery. Thus, understanding the role and dynamic changes of IDO in the perioperative period is important for optimizing patient outcomes. Methods: Patients with non-small cell lung cancer (NSCLC) who underwent surgery were enrolled in this study prospectively. Peripheral blood at different time points: preoperative, post anesthesia, post-vascular incision, post-tumor resection, and 3 days after surgery. The serum tryptophan and kynurenine were measured, and the kynurenine to tryptophan (K:T) ratio was used as an indicator of IDO activity. Paired Wilcoxon test was used to identify the significant difference of IDO activity at five different time points. The Kaplan–Meier log-rank test was used to assess the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Results: A total of 46 patients were enrolled in this study. The median follow-up time was 24.7 (range: 0.9 – 35.3) months. No patients died during the follow-up time. The PFS at 2 years was 76% (95% CI, 76%-100%). In all patients, IDO activity was not correlated significantly with better PFS. Surgical procedure does not affect levels of plasma IDO at any pathological stage in NSCLC significantly. The level of serum IDO of post-vascular incision was significantly correlated with that of 3 days after surgery (R 2 = 0.7, P &lt; 0.05). The level of preoperative level of serum kynurenine was significantly correlated with that of post-vascular incision and post-tumor resection (R 2 = 0.7/0.73, P &lt; 0.05). Conclusions: Surgical procedure does not have a significant effect on the serum IDO levels during the perioperative period. The perioperative levels of serum IDO are not correlated with the surgical prognosis of NSCLC, thus alternative markers are needed to better predict the surgical prognosis of NSCLC patients.
Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data.
Authors: Lorenzo Falchi, Michael Clausen, Fritz Offner, Sven de Vos, Joshua Brody, Kim M. Linton, Sylvia Snauwaert, Raul Cordoba, Jun Wu, Irina Bykhovski, Liwei Wang, Ali Rana, David Belada
Journal: Journal of Clinical Oncology (2023)

7519 Background: Patients (pts) with 1L diffuse large B-cell lymphoma (DLBCL) typically receive rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, around 40% relapse. Complete response rates and long-term outcomes are worse for high-risk pts with International Prognostic Index (IPI) 3–5 or double-hit/triple-hit lymphoma, representing an underserved pt population requiring better curative options. Data from the pivotal study of single-agent epcoritamab, a T-cell–engaging bispecific antibody, demonstrated impressive efficacy and a manageable safety profile (Thieblemont et al, JCO 2022). Preliminary data for epcoritamab + R-CHOP in 1L DLBCL (NCT04663347) showed encouraging efficacy. Here we present results for a larger cohort with longer follow-up. Methods: Pts with 1L CD20 + DLBCL and IPI ≥3 received subcutaneous epcoritamab (cycle [C] 1–4, QW; C5–6, Q3W) + R-CHOP for 6 Cs (21 d each) followed by epcoritamab monotherapy Q4W (28-d Cs) up to a total of 1 y. Results: As of Oct 31, 2022, 47 pts (median age, 64 y) had received epcoritamab 48 mg + R-CHOP with a median follow-up of 11.5 mo (range, 0.8–15.5). All pts had IPI 3–5, 37 (79%) had stage IV disease, and of 25 pts with FISH data available, 11 (44%) had double-hit/triple-hit DLBCL. Median time from diagnosis to first dose was 28 d (range, 3–423). Median dose intensity for R-CHOP was ≥95%. The most common treatment-emergent AEs (TEAEs) of any grade (G) were neutropenia (64%), anemia (62%), CRS (60%), fatigue (40%), pyrexia (40%), injection-site reactions (38%), and nausea (38%). TEAEs led to epcoritamab discontinuation in 3 pts; 1 pt had a G5 TEAE (COVID-19, unrelated to treatment). CRS was predominantly low grade (57% G1–2, 2% G3) and occurred mostly after the first full dose (C1D15); all cases resolved. One pt experienced G2 ICANS, which resolved. All response-evaluable pts (100%) had a response, and 76% had a complete metabolic response (CMR; Table). Notably, response rates were similar for double-hit/triple-hit pts (CMR rate, 82% [9/11]). The median durations of response, progression-free survival, and overall survival were not reached. Responses were durable; at 9 mo, an estimated 96% of pts with CMR remained in CMR. Updated data will be presented. Conclusions: Subcutaneous epcoritamab + R-CHOP induces high CMR rates with a manageable safety profile in pts with 1L high-risk DLBCL, including double-hit/triple-hit pts. These results support the ongoing phase 3 study of epcoritamab + R-CHOP in 1L pts (NCT05578976). Clinical trial information: NCT04663347 . [Table: see text]
A perilous and complicated situation in hospitals: Vitamin D deficiency in multiple myeloma patients—A nationwide cross-sectional study.
Authors: Manisha Rakesh Lakhanpal, Nikhila Chelikam, Divesh Manjani, Simmy Lahori, Sai Anusha Akella, Prashanth Gumpu Shivashankar, Shlok Vimal Shah, Abdirazak Ali, Varneet Toor, Aryak Singh, Rahul Gujarathi, Lokesh Manjani, Urvish Patel, Avinash Adiga, Geetika Kukreja
Journal: Journal of Clinical Oncology (2023)

e20010 Background: For the year 2019, the United States age-adjusted rate of new Multiple Myeloma (MM) cases was 6.8 per 100,000 people and the age-adjusted death rate was 3 per 100,000 people. Vitamin D Deficiency (VDD) and associated complications are very common in MM patients. Aim of our study was to evaluate the prevalence and risk of VDD in patients with MM and VDD associated disability and mortality in the VDD patients. Methods: We performed a cross-sectional retrospective analysis of Nationwide Inpatient Sample data 2016-2018. Adults hospitalizations with MM were identified using ICD 10 code. Hospitalized patients were grouped into patients with VDD and without VDD. We ran chi square, unpaired-t test and mixed-effect survey logistic regression analysis to find out odds ratio and 95%CI showing outcomes of VDD in MM patients. Results: We found 330,175 hospitalizations with MM. Of these 11,480 were noted to be patients with VDD with higher prevalence (0.64% vs 0.37%) of and strong association (aOR:1.41, 95%CI:1.35-1.47) with MM in comparison without MM. Amongst MM, females [1.50, 1.49-1.51], black race [1.23, 1.22-1.24], urban teaching hospitals [1.22, 1.22-1.23], and hospitals in mid-west region [1.30, 1.29- 1.32] had higher prevalence odds of VDD compared with males, white race population, rural hospitals and hospitals in northeast region. (p&lt;0.0001) Patients with VDD had higher prevalence and strong association with higher morbidity [5.1% vs 3.9%, 1.24,1.14-1.36; c-value=0.67], severe/extreme disability [77.2% vs 73.3%, 1.26, 1.20-1.33; c-value=0.73], and discharge to locations other than home [51.15% vs 45.69%, 1.29, 1.23-1.34; c-value=0.69] in comparison without VDD. (p&lt;0.0001) [Table]. Conclusions: Significant poor outcomes warrant early identification of VDD and role of same hospitalization vitamin D replacement amongst MM patients with higher risk. [Table: see text]
Post pandemic reality in breast cancer in Brazil.
Authors: Sabina B. Aleixo, Jose Zago Pulido, Narelle Parmanhane
Journal: Journal of Clinical Oncology (2023)

e22530 Background: After the coronavirus disease 2019 (COVID-19) pandemic, there was impact in breast cancer diagnosis all over the world but especially in low income countries. We aimed to evaluate the impact of COVID-19 pandemic on early diagnosis of breast cancer at an oncology center in southeast of Brazil. Methods: We extracted data on new breast cancer cases from Hospital Cancer Registry (RHC) of the Hospital Evangelico de Cachoeiro de Itapermirim in Espirito Santo/Brazil. Two intervals were compared: pre-COVID-19 (2019) and pos COVID-19 pandemic (2021) periods. Results: We had 224 new breast cancer cases in 2019 and 252 in 2021. There was an increase of 12,5 % new cases comparing the two years. In 2019 we had 23% of cases diagnosed in clinical stage (CS) I, 33% CS II, 15% CS III, 11% CS IV and 18% without information. In the year 2021 13% in CS I, 40% CS II, 20% CS III, 11% CS IV and 16% without CS information (table). In respect of age da median age at first diagnosis in 2019 was 61 years and in 2021 it was 56 years, demonstrating a decrease of age over the years. Conclusions: Breast cancer in Brazil was already a public health problem before the pandemic and it has aggravated. A substantial decrease in the number of patients with earlier stages of breast cancer at diagnosis was observed after COVID-19 pandemic. This studies demonstrates the need of efficient public policy to mitigate this problem. [Table: see text]
Aligning NCCN criteria with testing workflows using a novel database application (Criterion).
Authors: Rekha Sharma, Rena Vanzo, Tawanna St. Lewis, Cheryl Reeves, Pranav Mukund, Morgan Tolley, Poonam Sharma, Jivesh Sharma
Journal: Journal of Clinical Oncology (2023)

e22541 Background: As cost decreases and benefits become more well known, more individuals are seeking genetic testing. Physicians, genetic counselors, and other healthcare professionals play a critical role in explaining the benefits and limitations of genetic testing for hereditary cancer syndromes. Here we discuss our experience creating a web-based application, utilized by a variety of stakeholders, to determine whether patients are likely to meet clinical testing criteria set forth by the National Comprehensive Cancer Network (NCCN). Methods: To address the challenge of efficiently and accurately determining medical necessity for hereditary cancer genetic testing, we developed a pilot study to assess the utility of Criterion beta, a web-based pilot application. A questionnaire was sent to laboratory staff, genetic counselor assistants, genetic counselors, and physicians to assess the accuracy and usability of Criterion beta. 14 respondents each evaluated three mock patient profiles. They were initially asked to determine if the patients met current NCCN criteria for hereditary cancer genetic testing without using any alternative references or resources. Respondents with no prior training using Criterion were then asked to answer the exact same questions using Criterion beta. Results: Results of this pilot study indicate that implementation of Criterion beta leads to more accurate decision-making. Preliminary survey data shows that response accuracy for NCCN criteria determinations improved by 72% with the use of Criterion beta (see Figure 1). In addition, 85% of respondents reported that the application would allow them to routinely make more accurate decisions regarding who meets NCCN criteria for hereditary cancer genetic testing. Conclusions: As the demand for genetic testing increases, accessibility of professional guidelines like NCCN is important for multiple entities involved in the testing process, especially those unfamiliar with the concept of medical necessity. Clinically-based tools like Criteron beta are critical in this process because guidelines can be complex to navigate. In addition, through its ease of use, Criteron beta can better align implementation of genetic testing among high-risk populations. It may also place indirect pressure on industry stakeholders to align their eligibility requirements with clinical standards like NCCN, ultimately serving the best interests of patients in need of preventative care.
Clinical efficacy analysis of furmonertinib and structural insights into sensitivity to diverse TKIs for NSCLC with EGFR exon 20 insertion.
Authors: Xiao Zhang, Guoxing Feng, Baoxing Liu, Huan Han, Bosheng Dong, Yanfang Yang, Hui Zhu, Huijuan Wang, Saijun Fan, Hong Tang
Journal: Journal of Clinical Oncology (2023)

e21084 Background: Currently approved EGFR TKIs have dissatisfactory efficacy in most advanced NSCLC with EGFR exon 20 insertion mutations (EGFRex20ins). Whereas，preclinical studies have shown that furmonertinib demonstrated significantly antitumor activity in NSCLC with EGFRex20ins in vitro and in vivo. Here, we analyzed the clinical efficacy of furmonertinib in patients(pts) who harboring EGFRex20ins and explored mechanism. Methods: A retrospective single-arm analysis was performed to evaluate the efficacy of 20 NSCLC pts harboring EGFRex20ins receiving furmonertinib treatment who were determined at three institutions between Feb 2021 to Jul 2022. ORR, DCR, PFS, DOR and OS were analysed. The last follow-up time was February 1, 2023. Meanwhile, we investigated the clinical efficacy of furmonertinib (8 pts) versus osimertinib (8 pts) as second-line treatment, because pts about furmonertinib as first-line treatment were immature. In addition, the binding activity of different EGFR TKIs to EGFRex20ins were computationally constructed based on the crystal structure of EGFR_D770_N771insNPG/V948R (PDB ID: 7LGS) by the Schrödinger software (2021-2 Release, Schrödinger Inc., Portland, Oregon). Results: There are 10 (50.0%) females and the median age was 51 (32-77) years old. Of the 20 pts selected, we found that EGFRex20ins p.S768_D770dup (n = 5) variants were more common. We observed 14 pts with PR and six pts with SD as best response to furmonertinib (ORR: 70.0%, DCR: 100%). All pts showed tumor shrinkage in target lesions (median best percent change, -36.43% [-74.78%, -5.56%]). Median PFS was 10.2 (95 % CI, 7.00-13.40) months(mo). Median DOR was 8.5 (95 % CI, 5.08-11.92) mo. 13 pts were still alive by the last follow-up date. Comparative analysis of the efficacy of different groups showed that median PFS was significantly longer in furmonertinib group than in osimertinib (10.2 vs 3.8 mo, p = 0.008). Median OS was numerically longer in furmonertinib group than in osimertinib (18.9 vs 11.7 mo, p = 0.148). No grade 3 or above adverse events were observed. Furthermore, rather than erlotinib (GlideScore: -5.564; MM/GBSA: -52.8044), gefitinib (-7.68; -47.317), and afatinib (-5.075; -44.64), furmonertinib (-11.085; -68.1575) and osimertinib (-10.031; -63.87) revealed favorable binding activity to EGFRex20ins, with furmonertinib being the most significant. Conclusions: Furmonertinib might have positive clinical efficacy to advanced NSCLC pts with EGFRex20ins on account of its favorable binding activity to EGFRex20ins. It may be the optimal choice for these pts in the future.
Risk of further progression or death among durable progression-free survivors with melanoma in PD-1 blockade trials: Implications for imaging surveillance.
Authors: Lei Deng, Changchuan Jiang, Kristopher Attwood, Stuthi Perimbeti, Chen Hu, Igor Puzanov
Journal: Journal of Clinical Oncology (2023)

9529 Background: Durable progression-free survivors (dPFSors) over 2 years have been reported among melanoma patients treated with PD-1 blockade. However, non-negligible risk of further progression still exists and the optimal imaging surveillance interval is unknown. Methods: Individual patient data of progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with follow-up of at least 5 years of PFS events. Co-treatment with anti-CTLA4 antibody was allowed. Patients with PFS of at least 2 years were considered as dPFSors. Conditional risk of progression or death with 95% CI was estimated based on a piece-wise exponential survival model, with the assumption that within each year from the beginning of the third year, the risk of progression/death (P/D) was constant. Conditional risks of P/D every 3, 4, 6, and 12 months in each subsequent year were calculated with 95% confidence interval (CI). We pre-specified three maximal risk levels – 10%, 15%, and 20% at each imaging scanning interval. An interval is considered as acceptable if the 95% CI upper bound of the risk at each scan is lower than a pre-specified risk level. Results: Of 1495 melanoma patients from 3 clinical trials, 474 (31.7%) were dPFSors. Among them, the PFS probability for additional 3 years was 76.4%. During the 3 years, no more than 5.0% of patients had P/D in any quarters. The yearly risk of P/D was 15.5% (95% CI 13.7% - 17.3%), 8.8% (6.8% - 10.8%), and 6.3% (3.8% - 8.8%) during the 3rd, 4th, and 5th year, respectively. Under risk at 10%, 15%, and 20%, melanoma dPFSors can be scanned every 6, 6, and 12 months during the 3rd year, every 6, 12, and 12 months during the 4th, and every 12, 12, and 12 months during the 5th, respectively. Conclusions: Based on their own risk tolerance level, our findings allow clinicians and dPFSors make data-driven decisions regarding imaging surveillance schedule beyond every 3 months. [Table: see text]
Outcomes in patients with advanced gastrointestinal stromal tumor who did not have baseline ctDNA detected in the INTRIGUE study.
Authors: Jonathan C. Trent, Robin Lewis Jones, Suzanne George, Hans Gelderblom, Patrick Schöffski, Margaret von Mehren, John Raymond Zalcberg, Yoon-Koo Kang, Albiruni Ryan Abdul Razak, Steven Attia, Axel Le Cesne, William Reichmann, Kam Sprott, Haroun Achour, Matthew L. Sherman, Rodrigo Ruiz-Soto, Jean-Yves Blay, Michael C. Heinrich, Sebastian Bauer
Journal: Journal of Clinical Oncology (2023)

11536 Background: Ripretinib is a switch-control tyrosine kinase inhibitor approved for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with ≥3 kinase inhibitors, including imatinib. Exploratory baseline circulating tumor DNA (ctDNA) next-generation sequencing (NGS) analysis from INTRIGUE showed pts with second-line advanced GIST with primary KIT exon 11 mutations and secondary resistance mutations exclusively in KIT exons 17/18 derived clinical benefit from ripretinib but not sunitinib (Bauer S et al. J Clin Oncol. 2023; Abs 397784). Outcomes in pts with advanced GIST with ctDNA not detected (ctDNA-ND) had not been evaluated. Here, we present exploratory data from INTRIGUE in pts who had baseline ctDNA-ND vs ctDNA detected (ctDNA-D). Methods: INTRIGUE is an open-label, phase 3 study that enrolled pts with advanced GIST who had disease progression on or intolerance to imatinib (NCT03673501). Pts were randomized 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off) and stratified by mutation according to local pathology report. Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA NGS-based assay. Pts with ctDNA-D had ≥1 somatic alteration in the 74 genes analyzed. Results: Pts with ctDNA-ND (82/362, 22.7%) were younger (median: 55.5 vs 62.0 years) and had smaller sums of longest diameters of target lesions (median [range]: 57.6 [11–459] vs 108.8 [15–418] mm) vs ctDNA-D (280/362, 77.3%). Progression-free survival (PFS) was longer in pts with ctDNA-ND vs ctDNA-D and numerically higher with ripretinib vs sunitinib in pts with ctDNA-ND (Table). Pts with ctDNA-ND categorized as not having a KIT exon 9 mutation at randomization ( KIT exon 11, other KIT/PDGFRA, or KIT/PDGFRA wild-type; n = 71) had longer PFS with ripretinib vs sunitinib (median not estimable [NE] vs 11 months; HR = 0.56; 95% CI 0.28 to 1.12). Objective response rate (ORR) and overall survival (OS) were higher with ctDNA-ND vs ctDNA-D. Safety was similar between groups and consistent with the primary analysis. Conclusions: Pts with ctDNA-ND had better efficacy outcomes vs pts with ctDNA-D in both treatment arms; PFS was numerically higher with ripretinib vs sunitinib in pts with ctDNA-ND. Although little is known about the biology driving ctDNA in GIST, these data suggest pts may have improved outcomes and different treatment sensitivity based on ctDNA detectability. Clinical trial information: NCT03673501 . [Table: see text]